Giuseppe Maccarrone

Application of charged single isomer derivatives of cyclodextrins in capillary electrophoresis for chiral analysis

The review focuses on the role of ionic or ionisable single isomer derivatives (SIDs) of cyclodextrins on the separation of chiral analytes in capillary electrophoresis (CE), covering the period since the year 2000. The advantages of using pure compounds are discussed, as well as the ways to optimise the separations in the context of a rational approach to these techniques. Specific attention is paid to the modulation of the selector-analyte interaction. The advantage due to a detailed knowledge of equilibria occurring in solution during the CE run is underlined, particularly in the case of the presence of metal complexes, as occurs in chiral ligand exchange capillary electrophoresis (CLECE).

Potentiometric, spectroscopic and antioxidant activity studies of SOD mimics containing carnosine

Stability constant values and bonding details of the copper(II) complexes of the β-cyclodextrin functionalized with the carnosine dipeptide (β-alanyl-L-histidine) at its narrow (CDAH6) or at its wide (CDAH3) rim were determined in aqueous solution. The potentiometric and spectroscopic data (UV-vis, CD and EPR) show that the involvement of a secondary OH group induces drastic differences in the coordination properties of CDAH3, in comparison with those of CDAH6. Direct and indirect assays were carried out showing that the copper(II) complexes with the two cyclodextrin derivatives are SOD-mimics with high catalytic activity. In addition the complex species are scavenger compounds towards ˙OH radicals, giving rise to a particular kind of copper(II) complexes with a combined activity against two toxic radical species, O2˙− and ˙OH. The cyclodextrin moiety contributes to the scavenger activity, without damaging the cellular membranes of neuronal and red blood cells.

Coordination properties of 6-deoxy-6-[1-(2-amino) ethylamino]-β-cyclodextrin and the ability of its copper(II) complex to recognize and separate amino acid enantiomeric pairs

The functionalized cyclodextrin 6-deoxy-6-[1-(2-amino)ethylamino]-β-cyclodextrin was synthesized, and an NMR, EPR, pH-metric, and calorimetric investigation was carried out in aqueous solution in order to ascertain its behaviour towards protonation and copper(II) complex formation. The thermodynamic parameters of the ternary complex formation with alanine, phenylalanine and tryptophan enantiomeric pairs were also determined (25° C andI=0.1 mol dm−3). No thermodynamic enantioselectivity was observed in these systems, while a chiral, though poor, discrimination was observed in LEC: c.d. spectra also show enantiomeric stereoselectivity. The results of the present investigation, compared with previously reported results, suggest the occurence of acis-complex ⇆trans-complex equilibrium in such systems.

Recent advances in chiral separation of amino acids using capillary electromigration techniques.

This review highlights recent progresses in the chiral recognition and separation of amino acid enantiomers obtained by capillary electromigration techniques, using different chiral selectors and especially cyclodextrins, covering the literature published from January 2010 to March 2014. Sections are dedicated to the use of derivatization reagents and to the possibility to enantioseparate underivatized amino acids by using either ligand exchange capillary electrophoresis (LECE) and capillary electrophoresis (CE) coupled on line with mass spectrometry. A short insight on frontier nanomaterials is also given.

A Lewis Basicity Scale in Dichloromethane for Amines and Common Nonprotogenic Solvents Using a Zinc(II) Schiff-Base Complex as Reference Lewis Acid

A consistent, reliable scale of Lewis basicity in dichloromethane for 26 bases, involving amines and nonprotogenic solvents, is presented. A Lewis acidic Zn(II) Schiff-base complex, involving formation of stable 1:1 adducts is used as reference acid. Evaluation of binding constants is achieved from spectrophotometric titrations, by the least-squares nonlinear regression of multiwavelength spectrophotometric data. This Lewis basicity scale represents a unique set of data reflecting the actual Lewis basicity with respect this real world Lewis acidic species. The comparison of present Lewis basicity scale with data reported in the literature indicates that while for the involved solvents their relative basicity is scarcely affected by the reference Lewis acid, in contrast for sterically encumbered amines the Lewis basicity seems to be dependent from the reference species. Thus, Lewis basicity is governed by the steric hindrance at the donor atom and involves very different relative basicities than those predicted considering typical reference Lewis acids. This is expected to have a major involvement in the organic synthesis and catalysis, given the sterically encumbered nature of commonly involved Lewis acidic organometallic complexes.

Copper(II) complexes with chicken prion repeats: influence of proline and tyrosine residues on the coordination features.

The prion protein (PrPc) is a copper-binding glycoprotein that can misfold into a β-sheet-rich and pathogenic isoform (PrPsc) leading to prion diseases. The first non-mammalian PrPc was identified in chicken and it was found to keep many structural motifs present in mammalian PrPc, despite the low sequence identity (approximately 40%) between the two primary structures. The present paper describes the synthesis and the coordination properties of some hexapeptide fragments (namely, PHNPGY , HNPGYP and NPGYPH) as well as a bishexapeptide (PHNPGYPHNPGY), which encompasses two hexarepeats. The copper(II) complexes were characterized by means of potentiometric, UV–vis, circular dichroism and electron paramagnetic resonance techniques. We also report the synthesis of three hexapeptides (PHNPGF, HNPGFP and NPGFPH), in which one tyrosine was replaced by phenylalanine as well as two bishexapeptides in which either one (PHNPGFPHNPGY and PHNPGYPHNPGF), or two tyrosines were replaced by phenylalanine, in order to check whether tyrosine was involved in copper(II) binding. Overall, the results indicate that the major copper(II) species formed by the chicken PrP dodecapeptides are stabler than the analogous species reported for the peptide fragments containing two octarepeat peptides from the mammalian prion protein. It is concluded that the presence of four prolyl residues, that are break points in copper coordination, induces the metal-assisted formation of macrochelates as well as the formation of binuclear species. Furthermore, it has been shown that the phenolic group is directly involved in the formation of copper binuclear species.

Copper(II) complexes with l-lysine and l-ornithine: is the side-chain involved in the coordination?: A thermodynamic and spectroscopic study

Abstract The involvement of the ω-NH 2 terminal group of l -lysine and l -ornithine in the complexation of Cu(II) was investigated by means of potentiometry, calorimetry, UV–Vis and ESR. The thermodynamic parameters (Δ G 0 , Δ H 0 and Δ S 0 ) obtained by combining the potentiometric and calorimetric data show that the two ligands complex copper(II) in a different manner, indicating that the ω-NH 2 terminal group is involved in ornithine complexes only. UV–Vis and ESR spectra further support the involvement of ornithine ω-NH 2 and provide details on the complexation geometries of the complexes of the two amino acids.

Ligand exchange chiral separations by cyclodextrin derivatives in capillary electrophoresis

A beta-cyclodextrin substituted by an imidazole-bound histamine (CDmh) was successfully used to separate underivatised tryptophan racemate in capillary electrophoresis in the presence of copper(II) ion by the ligand exchange mechanism. To the best of our knowledge, this is the first example of a cyclodextrin derivative behaving as the first coordination sphere ligand in the complex added to the background electrolyte (BGE).

Chiral recognition by the copper(II) complex of 6-deoxy-6-N-(2-methylaminopyridine)-beta-cyclodextrin.

A modified beta-cyclodextrin bearing a 2-aminomethylpyridine binding site for copper(II) (6-deoxy-6-[N-(2-methylamino)pyridine)]-beta-cyclodextrin, CDampy) was synthesized by C6-monofunctionalization. The acid-base properties of the new ligand in aqueous solution were investigated by potentiometry and calorimetry, and its conformations as a function of pH were studied by NMR and circular dichroism (c.d.). The formation of binary copper(II) complexes was studied by potentiometry, EPR, and c.d.. The copper(II) complex was used as chiral selector for the HPLC enantiomeric separation of underivatized aromatic amino acids. Enantioselectivity in the overall stability constants of the ternary complexes with D- or L-Trp was detected by potentiometry, whereas the complexes of the Ala enantiomers did not show and difference in stability. These results were consistent with a preferred cis coordination of the amino group of the ligand and of the amino acid in the ternary complexes (cis effect), which leads to the inclusion of the aromatic side chain of D-Trp, but not of that of L-Trp. In Trp-containing ternary complexes, the two enantiomers showed differences in the fluorescence lifetime distribution, consistent with only one conformer of D-Trp and two conformers of L-Trp, and the latter were found to be more accessible to fluorescence quenching by acrylamide and KI.

Copper(II) complexes with an avian prion N-terminal region and their potential SOD-like activity

Potentiometric and spectroscopic (UV-Vis, CD and EPR) studies were carried out on copper(II) complexes with chicken prion protein N-terminal fragments, Ac-(PHNPGY)(4)-NH(2), and the mutated residue, Ac-(PHNPGF)(4)-NH(2), to assess the role of tyrosine in the copper coordination. Both thermodynamic and spectroscopic results indicate that chicken prion fragments are not able to bind more than two copper ions and only with the involvement of side chain tyrosine groups. The prevailing complex shows one copper ion bound to four imidazole nitrogen atoms in the 1:1 metal to ligand ratio systems. The superoxide dismutase (SOD)-like activity of copper(II) complexes with the avian peptides and mammal analogue, Ac-(PHGGGWGQ)(4)-NH(2), was also investigated by means of Pulse radiolysis. The copper(II) complexes with avian peptides do not display SOD-like activity, while very low activity has been detected for the copper(II) complexes with mammalian tetraoctarepeat.